The Developmentally Regulatedalb1Gene ofAspergillus fumigatus: Its Role in Modulation of Conidial Morphology and Virulence

Abstract

Aspergillus fumigatus, an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a putative polyketide synthase, and disruption ofalb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. Thealb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating thatalb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that thealb1 disruptant exhibited a smooth conidial surface, whereas complementation of the alb1 deletion restored the echinulate wild-type surface. Disruption of alb1 resulted in a significant increase in C3 binding on conidial surfaces, and the conidia of the alb1 disruptant were ingested by human neutrophils at a higher rate than were those of the wild type. Thealb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, thealb1 disruptant had a statistically significant loss of virulence compared to the wild-type and alb1-complemented strains in a murine model. These results suggest that disruption ofalb1 causes pleiotropic effects on conidial morphology and fungal virulence.

Aspergillus fumigatusMedA governs adherence, host cell interactions and virulence

“…It is also possible, although less likely, that other MedA-dependent factors are responsible for mediating the reduced virulence of this strain. Conidia of the DmedA mutant displayed alterations in pigmentation, a phenotype that has been linked to virulence previously (Tsai et al, 1998;1999). However, we observed that swollen conidia of the DmedA mutant, which do not contain pigment, were even less virulent in Galleria than were quiescent conidia (data not shown).…”

PKSP-dependent reduction of phagolysosome fusion and intracellular kill ofAspergillus fumigatusconidia by human monocyte-derived macrophages

“…Recently, we and others have shown that conidia, lacking pigmentation due to a mutated pksP gene (polyketide synthase involved in pigment biosynthesis), were less resistant to attack by monocytes in vitro , and showed reduced virulence in a murine animal model (Jahn et al ., 1997;Tsai et al ., 1998;Brakhage et al , 1999). To investigate whether the presence of a functional pksP gene affects intracellular processing of ingested conidia by macrophages, both A. fumigatus wild-type and pksP mutant conidia were analysed with respect to phagolysosome formation and intracellular kill in macrophages.…”

Identification and linkage mapping of the phsA gene of Aspergillus nidulans, where mutation affects growth and pigmentation of colonies in a temperature- and pH-dependent way

“…Some environmentally regulated genes a¡ecting growth have been described in the genus Aspergillus [17,18]. Recent work has suggested that the alb1 gene of A. fumigatus, which is involved in melanin biosynthesis, has a role in the modulation of virulence [19]. We believe that further characterization of strain phsA1 will clear up the role of this temperature-and pH-regulated response gene that is also involved in production of a melanin-like pigment in A. nidulans.…”